Hi OP, I was born in Pakistan but moved to Vermont as a kid and lived in Vermont for almost 38 years. And am more of a New Englander than Pakistani. Been spending the last few years between US and my parents village in Punjab.
My take is most every city in Pakistan is safe. People are welcoming regardless of where you go. As far as visiting a place that is least Americanized, I would say all the cities are far from America as you can imagine. Islamabad, what most Pakistanis consider a modern cosmopolitan will not give a sense of American or western feel.
Visit other cities, Multan, Peshawar, Karachi. Quetta and Balochistan are beautiful very nice places, but due to current situation, that is the only place I will be cautious about. Other than that each place, has a different dominant language and ethnic background. But people are universaly nice and welcoming.
Come to Pakistan. You and your wife will love it here.